Search Results (2,779)

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

Conventional semen analysis fails to capture the molecular determinants underlying impaired reproductive function. Emerging evidence positions seminal plasma (SP) and extracellular vesicles (EVs) as dynamic regulators of sperm physiology, rather than passive transport components. SP, enriched with proteins, metabolites, hormones, and antioxidants, modulates sperm motility, capacitation, acrosome reaction, and immune tolerance. Complementarily, EVs, including prostasomes, epididymosomes, and testicular vesicles, deliver proteins, lipids, and small RNAs that remodel sperm membranes, protect against oxidative insults, and influence fertilization success. A critical dimension of the SP-EV axis is its role in balancing oxidative stress (OS) and endocrine signaling. Hormones and metabolic regulators within SP, together with EV-mediated transfer of receptors and regulatory RNAs, further integrate systemic metabolic health with local reproductive outcomes. Dysregulation of these networks, particularly in conditions such as varicocele, obesity, diabetes, and idiopathic infertility, compromises sperm function and reduces assisted reproductive technology (ART) success. This evidence-based review synthesizes current evidence on SP and EVs as ‘molecular gatekeepers’ in male infertility, emphasizing OS regulation, endocrine crosstalk, and their potential as biomarker reservoirs. By integrating proteomic, metabolomic, and transcriptomic insights, the translational opportunities for biomarker-informed diagnostics, prognostication, and therapeutic interventions are highlighted. Full article

The inner spacer module, which profoundly affects the final performance of a device, is a critical component in GAA NSFET (Gate-all-around Nanosheet Field Effect Transistor) manufacturing and necessitates systematic optimization and fundamental innovation. This work aims to develop an advanced SiGe etching process with high selectivity, uniformity and low damage to achieve an ideal inner spacer structure for logic GAA NSFETs. For three distinct dry etching technologies, ICP (Inductively Coupled Plasma Technology), RPS (Remote Plasma Source) and Gas Etching, we evaluated their potential and comparative advantages for inner spacer cavity etching under the same experimental conditions. The experimental results demonstrated that Gas Etching technology possesses the uniquely high selectivity of the SiGe sacrificial layer, making it the most suitable approach for inner spacer cavity etching to reduce Si nanosheet damage. Based on the results, in the stacked structures, the SiGe/Si selectivity ratio exhibited in Gas Etching is ~9 times higher than ICP and ~2 times higher than RPS. Through systematic optimization of pre-clean conditions, temperature and chamber pressure control, we successfully achieved a remarkable performance target of cavity etching: the average SiGe/Si etching selectivity is ~56, the inner spacer shape index is 0.92 and the local etching distance variation is only 0.65 nm across different layers. These findings provide valuable guidance for equipment selection in highly selective SiGe etching and offer critical insights into key process module development for GAA NSFETs. Full article

The objective of the current research was to evaluate the influence of dietary tributyrin (TB) inclusion on the growth performance and physiological well-being of Hexagrammos otakii. Juvenile fish (initial weight 24.01 ± 1.35 g) were fed one of six isonitrogenous and isolipidic diets containing graded levels of TB (0–1.5 g/kg) for 90 days. Supplementation significantly enhanced the weight gain and specific growth rates. The optimal level of 0.9 g/kg TB improved muscle nutritional quality, muscle texture, and intestinal morphology. This dosage also significantly increased hepatic and intestinal antioxidant capacity, elevating superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC), while reducing malondialdehyde (MDA) content. Furthermore, dietary TB at 0.9 g/kg reduced plasma and hepatic triglycerides and total cholesterol, and elevated key plasma immune parameters, including complement components (C3, C4) and phosphatase activities (ACP, AKP). Intestinal health was further enhanced, as evidenced by increased digestive enzyme activities (amylase, lipase, chymotrypsin) and improved microbial diversity, marked by a proliferation of beneficial bacteria. In conclusion, dietary TB supplementation at 0.9 g/kg optimally promotes growth, improves muscle and intestinal health, and enhances antioxidant and immune functions in H. otakii. Full article

Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have uncovered novel mechanisms, such as mitochondrial transfer from platelets to target cells and the delivery of bioactive microRNAs that regulate inflammation and metabolic reprogramming. However, despite its potential, PRP therapy is often limited by inconsistent results. In this review, we examine how patient-specific factors—including age, comorbidities, and lifestyle—and technical variables in preparation and storage, influence the biological quality of the final product. Therefore, standardizing protocols and accounting for individual biological variability are essential for achieving reproducible outcomes. In conclusion, PRP is a complex therapeutic agent whose success depends on both intrinsic bioactive content and extrinsic processing factors. Integrating these molecular insights with personalized patient assessment is crucial to optimizing PRP treatment procedures. Future research should focus on refining standardization to fully establish PRP as a precision medicine tool in regenerative therapy. Full article

The saw-scaled viper Echis carinatus, one of the “Big Four” causes of snakebites in India, is found from Sri Lanka to eastern Iraq. To investigate clinical reports regarding the limited efficacy of Indian polyvalent antivenom (IPAV) against envenomation in Echis carinatus sochureki (ECS) in northwestern India, we obtained 22 snakes from three locations in Rajasthan and identified 148–174 toxin isoforms belonging to 21–25 toxin families in their venom using a bottom-up proteomics approach. All samples showed a high abundance of snake venom metalloproteinases (SVMPs), particularly SVMP class III. Other major components were phospholipases A₂, L-amino-acid oxidases, snake venom serine proteases and snaclecs (C-type lectins). Variation in venom composition among locations in Rajasthan, compared to E. c. carinatus (ECC) from southern India, was primarily due to differences in the relative abundance of these toxin families. Recognition of all venom components by IPAV was poor at lower antivenom concentrations. Notably, SVMP classes II and III were poorly recognized at all venom-to-antivenom ratios in all ECS venoms, and a plasma clotting assay revealed poor neutralization of procoagulant activity. This collaborative study highlights the need for the development of regional antivenoms to effectively treat snakebites in northwestern India. Full article

Titanium (Ti) and its alloys are widely used in biomedical applications due to their biocompatibility and corrosion resistance; however, surface modifications are required to enhance biological functionality. Surface functionalization using natural biomolecules has emerged as a promising strategy to improve early cell–surface interactions and biocompatibility of implant materials. In this study, Ti6Al4V alloy surfaces were biofunctionalized using Spirulina platensis (S. platensis) biomass and protein extract to evaluate morphological, chemical, and biological effects. The functionalization process involved activation with piranha solution, silanization with 3-aminopropyltriethoxysilane (APTES), and subsequent biomolecule immobilization. Surface characterization by scanning electron microscopy (SEM), inductively coupled plasma mass spectrometry (ICP-MS), energy-dispersive X-ray spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR) confirmed the successful incorporation of microalgal components, including nitrogen-, phosphorus-, and oxygen-rich organic groups. Biomass-functionalized surfaces exhibited higher phosphorus and oxygen content, while protein-coated surfaces showed nitrogen-enrich chemical signatures, reflecting the distinct molecular compositions of the immobilized biomolecules. Cell adhesion assays demonstrated enhanced early cell attachment on biofunctionalized surfaces, particularly in samples functionalized with 5 g/L biomass for three hours, which showed significantly greater cell attachment than both the control and protein-treated samples. These findings highlight the complementary yet distinct roles of S. platensis biomass and protein extract in modulating surface chemistry and cell–material interactions, emphasizing the importance of tailoring biofunctionalization strategies to optimize early biological responses on titanium-based implants. Full article

Background/Objectives: Following the cessation of breastfeeding, cereal-based complementary foods are commonly introduced into the diet of infants. Among these products, dairy-free infant porridges constitute an important component of early complementary feeding. This study aimed to evaluate dietary exposure to selected essential (Zn, Fe, Mn, and Cu) and potentially toxic (Pb, Cd, and Hg) trace elements resulting from the consumption of dairy-free infant porridges by children aged six months and older. Products with different cereal compositions available on the Polish market were analyzed. Methods: Trace element concentrations were determined after microwave-assisted digestion using inductively coupled plasma atomic emission spectrometry (ICP-AES) and atomic absorption spectrometry for mercury (Hg-AAS). Results: A single recommended serving of dairy-free infant porridge contributed to the intake of essential trace elements, providing approximately 50% of the RDA for copper, 21% for zinc, 15% of the AI for manganese, and 5.7% of the RDA for iron. The concentrations of potentially harmful elements were low (Pb: 0.002–0.004 mg/kg; Cd: <0.001–0.003 mg/kg; Hg: <0.001–0.001 mg/kg). The estimated daily intake of these elements did not exceed 0.01 µg/kg body weight per day. Conclusions: Dairy-free infant porridges may contribute to the intake of essential trace elements in infants, while exposure to lead, cadmium, and mercury appears to remain low when products are consumed according to recommended serving sizes. Full article

Sex-specific factors can influence the onset and progression of osteoarthritis (OA), yet the molecular mechanisms underlying their impact remain poorly defined. This study investigated whether plasma microRNAs (miRNAs) correlate to sex-dependent OA progression, based on evidence of enhanced spontaneous osteoclastogenesis in peripheral blood mononuclear cells (PBMCs) derived from OA patients. miRNAs were evaluated on OA-plasma (n = 20 men, 20 women with knee OA; KL grade I–II) and their role on OA signaling was investigated through bioinformatic analysis. Seven miRNAs were identified as significantly upregulated in men’ vs. women’ samples: hsa-miR-107, hsa-miR-23a-3p, hsa-miR-103a-3p, hsa-let-7g-5p, hsa-miR-22-3p, hsa-miR-106a-5p, hsa-miR-142-3p, and were associated with OA-related tissues and pathways. Notably, two common targets were identified: Adenosine Triphosphate Citrate Lyase (ACLY), a key enzyme linking citrate metabolism to epigenetic regulation, and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), a component of the phosphatidylinositol-3-kinase PI3K/AKT/mTOR pathway. In men, increased miRNA expression may repress ACLY and PIK3R1, affecting catabolic gene expression, inflammation, and OA progression. Conversely, their lower expression in women may mitigate these effects by counterbalancing the OA-promoting influences driven by sex hormones. A functional validation is needed to confirm miRNA–ACLY/PIK3R1 interactions and their sex-specific roles in early OA pathophysiology. Full article

Torque Teno Virus (TTV), a common and genetically diverse component of the human virome, is not linked to any known disease but reflects immune status. Its plasma viral load has shown clinical relevance in solid organ transplant recipients, correlating it with immunosuppression when present at high levels. However, the clinical significance of TTV viral load in hematopoietic stem cell transplantation (HSCT) recipients is less understood. This systematic review aims to evaluate whether plasma TTV DNA load directly correlates with the degree of T-cell immune reconstitution after HSCT, supporting its potential role as a biomarker for immune competence. The study protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD420251116208) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-one studies were included. The results showed concordant data about TTV kinetics with peak levels reaching approximately between +90 to +120 days after transplantation. Contradictory results have instead been found for the association of TTV load with immune parameters (lymphocyte counts, viral opportunistic infection, and development of acute graft versus host diseases). Even if a low-risk bias assessment was classified in most studies (67%), it was possible to identify important clinical and methodological differences between them, which might account for the different findings observed. Therefore, future larger studies with standardized protocols are needed to assess whether TTV viral load can serve as a reliable tool for guiding clinical decisions in the context of HSCT. Full article

This paper presents a new, quick method for testing the content of magnetic forms of iron in organic soils. These forms are an important marker of changes occurring in the environment. This method is based on impedance spectroscopy of a measuring coil inside which the tested material is placed—the material serves as the core of the coil. Unlike EIS (electrochemical impedance spectroscopy), the new method does not use electrodes, is sensitive to magnetic forms of iron, and is non-contact (the measuring current does not flow through the tested material). The results of research on three materials, including brown peat and silt with plant detritus, are presented in this paper. The results showed that changes in the standardized components of the measuring coil impedance in the frequency range of 100–135 kHz enable the determination of the content of ferromagnetic iron oxide (Fe₃O₄). The proposed method is very sensitive to soil oxide content in the range of 0% to 8%. Additionally, elemental composition analysis was performed using ICP-AES (inductively coupled plasma–atomic emission spectroscopy), which allowed for comparison of iron and other metal content with impedance measurement results. The final results confirm the usefulness of impedance spectroscopy as a non-destructive method for studying sedimentary environments and assessing their mineral properties. Full article

Background: Pediatric Major Depressive Disorder (pMDD) is one of the leading causes of disability in adolescents. There is currently no single explanation that fully accounts for the cause of the disorder, but various factors, including dysregulation of the immune and stress responses, have been linked to its onset. Oxylipins and endocannabinoids, derived from metabolization of n-3 and n-6 polyunsaturated fatty acids (PUFAs), regulate inflammation and have been suggested to attenuate inflammation associated with depression. This study aims to understand whether adolescents with pMDD have altered baseline levels of oxylipins and endocannabinoids compared to healthy adolescents. Methods: In this case–control study, we measured 60 oxylipins and endocannabinoids in plasma from 82 adolescents with pMDD and their matching healthy controls. Results: A Principal Component Analysis revealed substantial variability within each group and only a moderate degree of separation between them. In a paired analysis, the lipid mediators of controls exhibited higher concentrations of n-6 PUFA-derived prostaglandins and thromboxanes (PGE2, PGD2, PGF2a and TXB2), n-3 PUFA-derived TxB3, and the endocannabinoids AEA, EPEA, and DHEA. In contrast, cases had higher concentrations of the n-6 PUFA-derived 6-keto-PGF1a and the n-3 PUFA-derived PGD3. In addition, we observed a higher percentage of oxylipins and endocannabinoids derived from DHA (5.65 ± 5.46% vs. 4.72 ± 4.94%) and AA (16.31 ± 11.10% vs. 12.76 ± 13.46%) in plasma from controls, in line with the higher DHA and AA levels observed in erythrocytes from controls compared to cases. Conclusions: Overall, our results show lower plasma levels of endocannabinoids and lower DHA- and AA-derived oxylipins in adolescents with pMDD, supporting their role in the pathophysiology of pMDD. To infer a causative role of the n-3 and n-6 PUFA-derived oxylipins and endocannabinoids in pMDD, an intervention study with n-3 PUFA supplementation and monitoring of oxylipins and endocannabinoids would be necessary. Full article

Background: Chronic nonbacterial prostatitis (CNP), the major subset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), imposes a substantial global burden yet lacks satisfactory therapies. Maizibizi Wan (MZBZ) has long been used clinically for prostatitis, but its pharmacodynamic substance basis and mechanisms remain unclear. Methods: Ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS) coupled with Global Natural Products Social Molecular Networking (GNPS) molecular networking profiled MZBZ constituents and rat plasma–exposed prototype components and metabolites was used. Based on blood-absorbable components, network pharmacology predicted core targets/pathways; representative interactions were validated by molecular docking. A λ-carrageenan–induced CNBP rat model underwent histopathology (H&E), serum cytokine assays (TNF-α, IL-1β, IL-6/IL-17), immunohistochemistry (COX-2, TNF-α, MMP-9), and Western blotting (P-p65/p65, p-AKT/AKT, COX-2, TGF-β1, BCL2). Results: A total of 188 chemical constituents were identified in MZBZ (79 flavonoids, 38 organic acids, 30 alkaloids, 15 phenylpropanoids, 7 steroids, 4 phenylethanoid glycosides, 15 others). A total of 35 blood-absorbable components (18 prototype components, 17 metabolites) were identified, mainly involving Phase I oxidation and Phase II glucuronidation/sulfation. Network analysis yielded 54 core targets enriched in NF-κB and PI3K/AKT signaling and apoptosis. Docking indicated stable binding of key flavonoids to COX-2, NFKB1, TNF, IL-6, and BCL2. In vivo, MZBZ ameliorated prostatic inflammation, reduced serum TNF-α/IL-1β/IL-6/IL-17 (p < 0.05 or p < 0.01); decreased P-p65/p65, p-AKT/AKT, COX-2, and TGF-β1; and increased BCL2 in prostate tissue. Conclusions: MZBZ exerts anti-CNBP effects via multi-component synergy (prototypes + metabolites) that suppresses inflammatory cytokines, modulates apoptosis, and inhibits NF-κB and PI3K/AKT pathways. These findings provide a mechanistic basis and quality control cues for the rational clinical use of MZBZ. Full article

Background/Objectives: Post-COVID-19 pulmonary fibrosis (PCPF) and idiopathic pulmonary fibrosis (IPF) exhibit significant clinical and pathophysiological overlap, suggesting convergent molecular pathways driving fibrosis. This prospective longitudinal study investigates the sustained dysregulation of matrix metalloproteinases (MMP)-2 and MMP-9 and its relationship with evolving systemic inflammation and endothelial dysfunction in convalescent COVID-19 patients, with comparative analysis to IPF. Methods: We conducted a prospective observational study of 86 patients at 6 and 12 months post-SARS-CoV-2 infection, stratified by high-resolution CT evidence of PCPF (FB+ group, n = 32) or absence of fibrosis (FB− group, n = 54). Gene expression of MMP-2 and MMP-9 in peripheral blood leukocytes and circulating levels of MMP-2, MMP-9, pro-inflammatory cytokines (TNF-α, IL-6), and endothelial dysfunction markers (Endothelin-1 [ET-1], adhesion molecules) were quantified via qRT-PCR and ELISA. A pre-pandemic healthy control group (HD, n = 20) and an IPF patient group (n = 10) served as comparators. Results: A significant, sustained elevation of MMP-2 and MMP-9 was observed in all post-COVID-19 patients versus HDs, most pronounced in the FB+ group and qualitatively similar to IPF. A critical divergence emerged: FB− patients showed resolution of systemic inflammation (reduced TNF-α, IL-6), whereas FB+ patients exhibited persistent cytokine elevation. Critically, a delayed, severe endothelial dysfunction, characterized by a profound surge in ET-1 and elevated adhesion molecules, manifested exclusively in the FB+ cohort at 12 months. Positive correlations linked plasma MMP-2/9 levels with ET-1 (r_s = 0.65, p = 0.004; r_s = 0.49, p = 0.009) and ET-1 with sICAM-1 (r_s = 0.68, p = 0.01). Conclusions: The development of PCPF is associated with a distinct pathogenic triad: sustained MMP dysregulation, failure to resolve inflammation, and severe late-phase endothelial dysfunction. The correlative links between these components suggest a self-reinforcing loop. This systemic signature mirrors patterns in IPF, underscoring shared final pathways in fibrotic lung disease and identifying the MMP–inflammation–endothelial axis as a promising target for biomarker development and therapeutic intervention. Full article

Platelet-rich fibrin (PRF) is widely used in regenerative dentistry and oral surgery for its ability to promote tissue healing and modulate cellular responses. However, PRF contains not only platelets but also leukocytes and plasma components, complicating efforts to define the specific contribution of platelets to its biological activity. To address this, we used washed, leukocyte-depleted platelets activated with thrombin to generate platelet-released supernatant (PRS), which was applied to gingival fibroblasts. RNA sequencing identified 147 upregulated and 39 downregulated genes (|log₂ fold change| ≥ 2, FDR < 0.001), including cytokines IL11 and CXCL8 previously associated with PRF, as well as mitosis-related genes such as centromere-associated proteins, cell division cycle proteins, kinesin-like proteins, and shugoshins, consistent with gene ontology analyses. Validation by RT-PCR and immunoassays confirmed robust upregulation of IL11 and CXCL8. Functionally, PRS activated TGF-β signaling, indicated by Smad2/3 nuclear translocation, but did not induce NF-κB signaling. These findings demonstrate that platelets are major contributors to PRF’s biological effects, independent of leukocytes and plasma, and elicit a pronounced mitogenic and TGF-β-dominant response in gingival fibroblasts. They also provide insight into the cellular mechanisms underlying PRF-mediated tissue regeneration. Full article